Background: Cell therapy using hepatocytes derived from stem cells has been regarded as a promising alternate to liver transplantation. However, the heterogeneity of these hepatocytes makes them unsuitable for therapeutic use. To overcome this limitation, we generated homogenous hepatocyte like induced hepatocyte-like (iHep) cells.
Methods: iHep cells were generated from induced pluripotent stem cells (iPSCs) integrated with the albumin (ALB) reporter gene. The therapeutic properties of these iHep cells were investigated after transplantation in fibrotic liver tissues of a mouse model.
Results: The iHep cells expressed hepatocyte specific genes and proteins, and exhibited high levels of hepatocyte growth factor (HGF) and interleukin (IL)-10 expressions. Transplantation of iHep cells significantly decreased thioacetamide (TAA)-induced liver fibrosis, apoptotic cells in the liver, and ameliorated abnormal liver function. Liver tissues engrafted with iHep cells exhibited decreased expression of pro-inflammatory factors such as transforming growth factor (TGF)-β, IL-6, and monocyte chemo attractant protein (MCP)-1. Furthermore, an increased number of proliferating hepatocytes and human albumin-expressing iHep cells were detected in mice liver.
Conclusions: This study has investigated and proven the liver regeneration potential of genome-edited iHep cells and promises to be a strong foundation for further studies exploring cell therapy as an alternative therapeutic option for the treatment of liver fibrosis.
Keywords: Albumin; Cell therapy; Differentiation; Gene editing; Hepatocyte; Knock-in; Liver cirrhosis; Reporter system; Stem cell; TALEN.